RETENTION OF CYTOKINE-INDUCING SUBSTANCES INSIDE HIGH-FLUX DIALYZERS

Reprocessing of dialyzers is often performed with nonsterile solutions possibly contaminated with bacterial-derived cytokine-inducing substa nces. We investigated the retention of cytokine-inducing substances in side the dialyzer during reprocessing in a closed loop in vitro hemodi alysis system using a polyamide high flux membrane. After the first in vitro circulation of human whole blood, rinse of the blood compartmen t (BC) and reverse ultrafiltration (RUF) was performed with either cyt okine-inducing substance-free saline or saline contaminated with filtr ates from Pseudomonas cultures (6 ng/ml LAL-reactive material); subseq uently, dialyzers were stored in 2% formaldehyde. Dialyzers were rinse d with approximately 15 liters pyrogen-free saline before the second c irculation using blood from the same donor; the effluates were free of cytokine-inducing substances and formaldehyde. Before and after the b lood circulations, peripheral blood mononuclear cells (PBMC) were sepa rated and total production of IL-1 alpha and IL-1 beta was determined after overnight incubation. In noncirculated PBMC as well as in PBMC s eparated after whole blood circulation with pyrogen-free processed dia lyzers, production of IL-1 beta was not detectable. After contaminated rinse of the BC, production of IL-1 beta could be observed (1,600 +/- 1,100 pg/ml, mean +/- SEM). When pyrogen-free RUF was performed after contaminated BC rinse, IL-1 beta production averaged 163 +/- 92 pg/ml when using reused dialyzers, but 1,820 +/- 880 pg/ml when using new d ialyzers. After reuse with pyrogen-free BC-rinse and contaminated RUF no IL-1 beta synthesis was observed; however, when pyrogen-free BC-rin se and contaminated RUF was applied to new dialyzers, IL-1 beta synthe sis averaged 1,620 +/- 1,200 pg/ml. We conclude that cytokine-inducing substances are retained inside the dialyzer, probably by adsorption t o the membrane as well as to the protein layer covering the membrane a nd are still biologically active after sterilisation. Cytokine-inducin g substances substances are retained inside the dialyzer, probably by adsorption to the membrane as well as to the protein layer covering th e membrane and are still biologically active after sterilisation. Cyto kine-inducing substances adsorbed to the protein layer can be partiall y removed by RUF. Finally, the protein layer on the membrane appears t o reduce the convective transfer of cytokine-inducing substances from the dialysate into the blood compartment.